Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses

doi:10.1016/j.jalz.2015.05.015

Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses

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Abstract

Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.

Original language	English
Pages (from-to)	1439-1451
Number of pages	13
Journal	Alzheimer's and Dementia
Volume	11
Issue number	12
DOIs	https://doi.org/10.1016/j.jalz.2015.05.015
State	Published - Dec 1 2015

Bibliographical note

Funding Information:
ACT: ACT is supported by a grant ( U01 AG 06781 , to E.B.L. and P.K.C.) from the National Institutes of Health .

Funding Information:
ROS/MAP: ROS and MAP are supported by National Institute on Aging grants R01AG17917 , R01AG34374 , R01AG15819 , and P30AG10161 (all to D.A.B.).

Funding Information:
The Health and Retirement Study genetic data are sponsored by the National Institute on Aging (grant numbers U01AG009740 , RC2AG036495 , and RC4AG039029 ) and was conducted by the University of Michigan.

Publisher Copyright:
© 2015 The Alzheimer's Association.

Keywords

Alzheimer's disease
Dementia
Mendelian randomization
Obesity

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jalz.2015.05.015

Cite this

@article{c0cff54ffdd942f49cde973061b77b54,

title = "Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses",

abstract = "Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.",

keywords = "Alzheimer's disease, Dementia, Mendelian randomization, Obesity",

author = "Shubhabrata Mukherjee and Stefan Walter and Kauwe, {John S.K.} and Saykin, {Andrew J.} and Bennett, {David A.} and Larson, {Eric B.} and Crane, {Paul K.} and Glymour, {M. Maria} and Albert, {Marilyn S.} and Albin, {Roger L.} and Apostolova, {Liana G.} and Arnold, {Steven E.} and Sanjay Asthana and Atwood, {Craig S.} and Baldwin, {Clinton T.} and Barber, {Robert C.} and Barmada, {Michael M.} and Barnes, {Lisa L.} and Beach, {Thomas G.} and Becker, {James T.} and Beecham, {Gary W.} and Duane Beekly and Bigio, {Eileen H.} and Bird, {Thomas D.} and Deborah Blacker and Boeve, {Bradley F.} and Bowen, {James D.} and Adam Boxer and Burke, {James R.} and Buxbaum, {Joseph D.} and Cairns, {Nigel J.} and Cantwell, {Laura B.} and Chuanhai Cao and Carlson, {Chris S.} and Carlsson, {Cynthia M.} and Carney, {Regina M.} and Carrasquillo, {Minerva M.} and Carroll, {Steven L.} and Chui, {Helena C.} and Clark, {David G.} and Jason Corneveaux and Cribbs, {David H.} and Crocco, {Elizabeth A.} and Carlos Cruchaga and {De Jager}, {Philip L.} and Charles DeCarli and Demirci, {F. Yesim} and Malcolm Dick and Jicha, {Gregory A.} and {Van Eldik}, {Linda J.}",

note = "Funding Information: ACT: ACT is supported by a grant ( U01 AG 06781 , to E.B.L. and P.K.C.) from the National Institutes of Health . Funding Information: ROS/MAP: ROS and MAP are supported by National Institute on Aging grants R01AG17917 , R01AG34374 , R01AG15819 , and P30AG10161 (all to D.A.B.). Funding Information: The Health and Retirement Study genetic data are sponsored by the National Institute on Aging (grant numbers U01AG009740 , RC2AG036495 , and RC4AG039029 ) and was conducted by the University of Michigan. Publisher Copyright: {\textcopyright} 2015 The Alzheimer's Association.",

year = "2015",

month = dec,

day = "1",

doi = "10.1016/j.jalz.2015.05.015",

language = "English",

volume = "11",

pages = "1439--1451",

number = "12",

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TY - JOUR

T1 - Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples

T2 - Mendelian randomization analyses

AU - Mukherjee, Shubhabrata

AU - Walter, Stefan

AU - Kauwe, John S.K.

AU - Saykin, Andrew J.

AU - Bennett, David A.

AU - Larson, Eric B.

AU - Crane, Paul K.

AU - Glymour, M. Maria

AU - Albert, Marilyn S.

AU - Albin, Roger L.

AU - Apostolova, Liana G.

AU - Arnold, Steven E.

AU - Asthana, Sanjay

AU - Atwood, Craig S.

AU - Baldwin, Clinton T.

AU - Barber, Robert C.

AU - Barmada, Michael M.

AU - Barnes, Lisa L.

AU - Beach, Thomas G.

AU - Becker, James T.

AU - Beecham, Gary W.

AU - Beekly, Duane

AU - Bigio, Eileen H.

AU - Bird, Thomas D.

AU - Blacker, Deborah

AU - Boeve, Bradley F.

AU - Bowen, James D.

AU - Boxer, Adam

AU - Burke, James R.

AU - Buxbaum, Joseph D.

AU - Cairns, Nigel J.

AU - Cantwell, Laura B.

AU - Cao, Chuanhai

AU - Carlson, Chris S.

AU - Carlsson, Cynthia M.

AU - Carney, Regina M.

AU - Carrasquillo, Minerva M.

AU - Carroll, Steven L.

AU - Chui, Helena C.

AU - Clark, David G.

AU - Corneveaux, Jason

AU - Cribbs, David H.

AU - Crocco, Elizabeth A.

AU - Cruchaga, Carlos

AU - De Jager, Philip L.

AU - DeCarli, Charles

AU - Demirci, F. Yesim

AU - Dick, Malcolm

AU - Jicha, Gregory A.

AU - Van Eldik, Linda J.

N1 - Funding Information: ACT: ACT is supported by a grant ( U01 AG 06781 , to E.B.L. and P.K.C.) from the National Institutes of Health . Funding Information: ROS/MAP: ROS and MAP are supported by National Institute on Aging grants R01AG17917 , R01AG34374 , R01AG15819 , and P30AG10161 (all to D.A.B.). Funding Information: The Health and Retirement Study genetic data are sponsored by the National Institute on Aging (grant numbers U01AG009740 , RC2AG036495 , and RC4AG039029 ) and was conducted by the University of Michigan. Publisher Copyright: © 2015 The Alzheimer's Association.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.

AB - Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.

KW - Alzheimer's disease

KW - Dementia

KW - Mendelian randomization

KW - Obesity

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UR - http://www.scopus.com/inward/citedby.url?scp=84952308113&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2015.05.015

DO - 10.1016/j.jalz.2015.05.015

M3 - Article

C2 - 26079416

AN - SCOPUS:84952308113

VL - 11

SP - 1439

EP - 1451

IS - 12

ER -

Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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